Method of heat sanitization of a haemodialysis water circuit using a calculated dose

ABSTRACT

A method of sanitizing liquid for use in a medical device, the method comprising the steps of providing a medical device defining a water circuit with a volume of liquid, sensing the temperature of the volume of liquid with a sensor, heating the volume of liquid from an initial temperature to exceed a threshold temperature, maintaining the volume of liquid above the threshold temperature, determining a time-temperature value for the volume of liquid periodically once the threshold temperature has been exceeded, calculating a cumulative time-temperature value and providing an output signal once the cumulative time-temperature value has reached a level indicative of a sanitizing dose. A medical device and a liquid sanitizer are also disclosed.

The present invention relates to the preparation of dialysis fluid forhemodialysis and related therapies and substitution fluid for use inonline therapies, such as hemodiafiltration and hemofiltration. Inparticular, the present invention relates to a method for heatsanitization of a liquid used in one of the above processes.

It is known to use heat to destroy microorganisms. During a thermaldestruction process, the rate of destruction of microorganisms islogarithmic, as is the rate of growth of the microorganisms. Thusbacteria subjected to heat are killed at a rate that is proportional tothe number of organisms present. The process is dependent both on thetemperature of exposure and the time required at this temperature toaccomplish to desired rate of destruction.

Thermal calculations thus involve the need for knowledge of theconcentration of organisms to be destroyed, the acceptable concentrationof organisms that can remain behind (spoilage organisms, for example,but not pathogens), the thermal resistance of the target organisms (themost heat tolerant ones), and the time-temperature relationship requiredfor destruction of the target organisms.

Disinfection of many water based systems in medical devices isfrequently achieved by elevating the temperature for a stipulated periodof time, thereby using heat to destroy the microorganism in the water.In dialysis it is common for a combination of 80 degrees Celsius (° C.)to be maintained for 30 minutes.

There are several well-established time-temperature relationships formoist heat disinfection which are regarded as equally acceptable. Formoist heat disinfection a particular time at a particular temperaturecan be expected to have a predictable lethal effect against astandardised population of organisms. It is therefore possible to definea standard exposure which will yield a disinfected product in acorrectly operated Washer Disinfector (WD). Actual exposures can then berelated to these standard exposure conditions.

Definition of such disinfection processes may be achieved by means ofthe A₀ method which uses a knowledge of the lethality of the particularprocess at different temperatures to assess the overall lethality of thecycle and express this as the equivalent exposure time at a specifiedtemperature.

The A value is a measure of the heat resistance of a microorganism.

A is defined as the equivalent time in seconds at 80° C. to give adisinfection effect.

The z value indicates the temperature sensitivity of the reaction. It isdefined as the change in temperature required to change the A value by afactor of 10.

When the z value is 10° C., the term A₀ is used.

The A₀ value of moist heat disinfection process is the equivalent timein seconds at a temperature of 80° C. delivered by that process to theproduct with reference to microorganisms possessing a z value of 10° C.

$A_{0} = {\sum{10^{\lbrack\frac{({T - 80})}{z}\rbrack}{dt}}}$

Where:

A₀ is the A value when z is 10° C.;t is the chosen time interval, in seconds;and T is the temperature in the load in ° C.

In calculating A₀ values a temperature threshold for the integration isset at 65° C. since for temperatures below 65° C. the z and D value ofthermophillic organisms may change dramatically and below 55° C. thereare a number or organisms which will actively replicate.

In dialysis current practice, raising the temperature to 80° C. for 30minutes gives a benchmark value A₀ equal to 1800.

The present invention aims to provide an efficient method of heatsanitization of a haemodialysis water circuit.

According to the first aspect of the present invention, there isprovided a method of sanitizing liquid for use in a medical device,comprising the steps of sensing the temperature of a volume of liquidwith a sensor; heating the volume of liquid from an initial temperatureto exceed a threshold temperature; maintaining the volume of liquidabove the threshold temperature; determining a time-temperature valuefor the volume of liquid periodically once the threshold temperature hasbeen exceeded; calculating a cumulative time-temperature value; andproviding an output signal once the cumulative time-temperature valuehas reached a level indicative of a sanitizing dose.

Calculation of the time-temperature value for the volume of liquid basedon the cumulative effect of heating the water provides a more accuratemodel of the sanitization process by ensuring a fixed dose of heatsanitization is applied to the volume of liquid. Furthermore, itmaximises the benefits of high temperatures (in particular those above80° C.) thereby reducing the time for which components are exposed toelevated temperatures. Natural variation in the control loop and waterrecirculation will cause natural temperature oscillations. Those timeperiods below 80° C. but above the minimum temperature range areintegrated into the dose and those above are not leveraged according tothe power law relationship.

The cumulative time-temperature value may be calculated by a processor.Alternatively, the cumulative time-temperature value may be calculatedfrom a lookup table.

The method may comprise the further step of setting a target cumulativetime-temperature value and providing the output signal once the targetcumulative time-temperature value is reached.

The output signal may be in the form of an audible or visual alarm. Thisinforms the user or operator that the sanitization process is complete.

The output signal may automatically cause termination of the liquidheating. This prevents the heat sanitization cycle from running forlonger than is necessary.

The method may comprises the further step of maintaining the volume ofliquid below an upper temperature. This may be to prevent boiling of thesanitizing liquid, or prevent unnecessary thermal stress on thecomponents of the heat sanitization device.

The method may comprise the further step of setting the thresholdtemperature. The method may comprise the further step of setting anoverall heating time. This allows the process to be tailored accordingto the environmental conditions (for example room temperature, liquidinput temperature) the situational conditions, (for example emergencyprocedure, routine procedure, clinic timetables) and the patient'sneeds. Thus the time and/or temperature may be selected withoutcompromising the dose of heat sanitization applied to the volume ofliquid.

The threshold temperature may be between 55° C. and 65° C.

The upper temperature may be between 70° C. and 99° C.

Multiple temperature sensors may be used to provide the temperature ofthe volume of liquid.

In one embodiment, the cumulative time-temperature value may becalculated according to

$A_{0} = {\sum{10^{\lbrack\frac{({T - 80})}{z}\rbrack}{dt}}}$

Where:

A₀ is the A value when z is 10° C.;t is the chosen time interval, in seconds;and T is the temperature in the load in ° C.

This allows the destruction of organisms at 65° C. to 80° C. to beincluded in the calculation of the cumulative time-temperature value.

The A₀ value may be equal to 1800.

According to a second aspect of the present invention, there is provideda liquid sanitizer comprising a tank containing a volume of liquid; asensor arranged to sense the temperature of the volume of liquid; aheater arranged to heat the volume of liquid from an initial temperatureto exceed a threshold temperature, and maintain the volume of liquidabove the threshold temperature; and a processor, wherein the processoris configured to determine a time-temperature value for the volume ofliquid periodically once the threshold temperature has been exceeded andcalculate a cumulative time-temperature value so as to provide an outputsignal once a cumulative time-temperature value indicative of asanitizing dose is reached.

The processor may be programmable to alter at least one of the thresholdtemperature and the cumulative time-temperature value.

According to a third aspect of the present invention, there is provideda dialyser incorporating the liquid sanitizer according to the secondaspect of the present invention.

An embodiment of the present invention will now be described, by way ofexample only, with reference to the accompanying figures, in which:

FIG. 1 is a schematic of a dialysis machine incorporating the liquidsanitizer;

FIG. 2 is a magnified detail view of the liquid sanitzer of FIG. 1;

FIG. 3 is a temperature profile of the liquid in a liquid sanitizerundergoing a typical sanitization cycle; and

FIG. 4 is a temperature profile of the liquid in the liquid sanitizer ofFIG. 1 undergoing a typical sanitization cycle.

Referring to FIG. 1, a dialysis machine 10 is shown having a main body12 and a hinged door 14. The door 14 is hinged so as to allow a dummydialysis cartridge 16 to be received between the main body 12 and thedoor.

The machine 10 has a blood pumping portion indicated generally at 9 forpumping patient blood to and from a dialyser (not shown for clarity) ina known manner. The main body 12 has a platen 21 behind which is anengine portion (not shown for clarity). The platen 21 is configured toreceive the dummy cartridge 16 within a recessed portion 25.

The engine portion includes a pneumatic pump for providing pressure andvacuum to operate the machine and a controller to control retention ofthe dummy cartridge 16 within the machine 10 and fluid flow on the dummycartridge 16 as will be discussed in further detail below.

The door 14 has an outer side including a user interface 2. The door 14includes an actuator in the form of an airbag (not shown), operable bythe engine portion to provide a closure load to close the dummycartridge 16 onto the platen 21 and to ensure that a continuous sealfully engages the dummy cartridge 16.

The dummy cartridge 16 will now be described in further detail. Thedummy cartridge 16 has a chassis defining a door side and a platen side.In use the platen side of the cartridge 16 engages the platen 21 on themain body 12 of the machine 10, and the door side engages an interfaceplate (not shown) on the door 14 of the machine 10.

The dummy cartridge 16 is formed from an acrylic such as SG-10 which ismoulded in two parts (a platen side and a patient side) before beingbonded together to form the chassis. Both the platen side and door sideare covered in a clear flexible membrane formed from, for example,DEHP-free PVC which is operable by pneumatic pressure applied to themembrane by the pneumatic compressor in the main body via the platen 21.In this way a series of flow paths 17 are formed in the cartridge forcarrying sanitizing water.

In use, the engine portion of the machine 10 applies either a positiveor negative pressure to the membrane via the platen 21 in order toselectively open and close valves and pumps to pump sanitizing fluidthrough the dummy cartridge 16, which is described in detail below.

The machine 10 has liquid sanitizer generally designated as 200. Thearrows on FIG. 1 show the sanitizing water flow path when the liquidsanitizer is in use.

With reference to FIG. 2, the liquid sanitizer will be described infurther detail.

The liquid sanitizer 200 has a tank 202, a heater 210 and a processor230. The tank 202 contains, in use, a volume of water 203.

The tank 202 has an inlet 204 and a drain 206. The inlet 204 isconnectable to a water source (not shown) and the drain 206 isconnectable to a waste pipe (also not shown). The tank 202 also has afeed pipe 220 connectable to the dummy cartridge 16 via the platen 21and a return pipe 224, also connectable to the dummy cartridge 16 viathe platen 21. Referring back to FIG. 1, the dummy cartridge 16 has asanitizing water circulation path 17 so as to complete a sanitizingwater circuit comprising the tank 202, feed pipe 220, dummy cartridge 16and return pipe 224.

The heater 210 has a heating element 212 arranged to heat the volume ofwater 203 contained within the tank 202, in this case by immersion inthe volume of water 203 in the tank 202. The heater 210 iselectronically connected to processor 230 by heater connector 211.

Temperature sensors are arranged on the sanitizing water circuit. Adriver temperature sensor 222 is arranged on the feed pipe 220 adjacentthe water tank 202. A return temperature sensor 226 is arranged on thereturn pipe 224 adjacent the water tank 202. A check temperature sensor228 is arranged on the return pipe adjacent, but offset from, the returntemperature sensor 226. All three temperature sensors are electronicallyconnected to the processor 230 via sensor connectors. Driver temperaturesensor 222 is electronically connected to processor 230 by sensorconnector 223. Return temperature sensor 226 is electronically connectedto processor 230 by sensor connector 227. Check temperature sensor 228is electronically connected to processor 230 by sensor connector 229.

The electronic connectors 211, 223, 228, 229 may be wired or wireless.The processor 203 may be remote to both the tank 202 and heater 210.

The processor 230 thereby controls both the heating of the water andreceives the temperature values for the sanitizing water circuit.

In use, the tank 202 of liquid sanitizer 200 is filled with the desiredquantity of water via inlet 204. This would typically be 500 ml, whichis the amount sufficient to flush out the water circuit of a kidneydialyser.

The liquid sanitizer is then turned on. The processor 230 activates theheater 210 to heat the volume of water via the heating element 221 andthe pump draws the water around the sanitizing water circuit. Thetemperature of the water exiting the tank 202 via feed pipe 220 isperiodically sensed by drive temperature sensor 222, and the temperaturedata is periodically sent to processor 230 via sensor connector 223. Thetemperature of the water returning to the tank 202 via return pipe 224is periodically sensed by return temperature sensor 226, and thetemperature data is periodically sent to processor 230 via sensorconnector 227. The processor 230 therefore periodically receives sensedtemperature data to provide a feedback loop to moderate the heating ofthe volume of water 203 to maintain the temperature of the volume ofwater 203 above a threshold temperature.

When the processor 230 receives data from the sensor 220 that the volumeof water 203 has exceeded the threshold temperature, the processor 230periodically samples the temperature of the volume of water via thereturn temperature sensor 226, which theoretically represents the lowestpossible temperature of the water on the sanitizing water circuit.

The value is checked by periodically sampling the temperature of thevolume of water via the check temperature sensor 228.

The sampling is performed periodically at, for example, 1 secondintervals. The sampling intervals may be varied as appropriate.

Each sampled temperature represents a time-temperature value, which canbe calculated by the processor 230, or alternatively generated by alook-up table.

The processor 230 calculates a cumulative time-temperature value for thevolume of liquid 20 by summing the sampled time-temperature values. Thisis compared to a target total time-temperature value indicative of asanitizing dose.

Once the calculated cumulative time-temperature value and the targetcumulative time-temperature value are equal, the processor 230 sends anoutput signal to indicate that a sanitizing dose has been reached. Theoutput signal is received by the heater and automatically switches offthe heater 210.

In an alternate embodiment, the processor 230 may switch off the waterheater 210 in advance of a sanitizing dose being reached, by calculatingthat there is sufficient thermal energy contained within the watercircuit that the water temperature will remain above the thresholdtemperature for long enough to ensure a sanitizing dose is reached. Inthat case, periodic sampling would be continued, such that the processor230 is able to send the output signal to indicate that a sanitizing dosehad indeed been reached.

The output signal is received by the LCD display unit, which displaysthe text “COMPLETE” in reference to the completed sanitizing dose. Inalternate embodiments, the LCD display unit includes an audible alarm.The audible alarm can be configured to bleep repeatedly until thesanitizer is turned off.

With reference to FIG. 3, a typical temperature profile 300 of the waterin a known liquid sanitizer is shown during a single disinfection cycle.

The water already contained within the tank is at room temperature 301(18° C.) initially. As cool fresh water is added from a tap to ensurethe correct quantity of water is provided in the tank (wherein the coolfresh water is typically 8° C.), the overall temperature of the liquidwill drop slightly 302.

The water temperature then rises substantially linearly towards thetarget temperature of 80° C. 305, which is reached at about 60 seconds.There is a slight oscillation 304 of about one and a half wavelengthswhere the water temperature exceeds and passes below 80° C. (toapproximately 85° C. and 75° C. respectively) as the water heater findsthe correct balance to maintain a constant water temperature of 80° C.After approximately 30 minutes at 80° C. the water heater is switchedoff 307 and the water temperature steadily decreases to room temperature(18° C.) 301.

With reference to FIG. 4 a typical temperature profile 400 of the waterin the liquid sanitizer 200 is shown during a single disinfection cycle.

Similar notable points on the temperature profile are given similarreference numerals as that for FIG. 3, prefixed by a “4” instead of a“3” to indicate that they represent the temperature profile 400 of thewater in the liquid sanitizer 200.

The initial drop in temperature 402 from room temperature 401 (18° C.)and subsequent heating of the water occurs following a similartime-temperature profile to that shown in FIG. 3.

However, when the temperature of the water exceeds the thresholdtemperature. 65° C. 403, the liquid sanitizer begins to record atime-temperature value.

Furthermore, when the target temperature 80° C. 405 is reached, thewater temperature is continually raised 406 such that a greatertime-temperature value contribution can be achieved with each sample.

The heater is switched off 407 after less than 8 minutes as there issufficient thermal energy within the water to ensure that a completesanitizing dose is achieved before the temperature of the water fallsbelow the threshold temperature of 65° C. 403.

The overall cycle time for the sanitizing dose is slightly more than 8minutes. This compares to the overall cycle time for a sanitizing doseaccording to the temperature profile of FIG. 3 of over 30 minutes.

An exemplary Lookup Table may include the following values for 1 secondsampled increments:

TABLE 1 Lookup Table Temperature Time-temperature (° C.) value 95 35.48194 28.184 93 22.387 92 17.783 91 14.125 90 11.22 89 8.913 88 7.079 875.623 86 4.467 85 3.548 84 2.818 83 2.239 82 1.778 81 1.413 80 1.122 790.891 78 0.708 77 0.562 76 0.447 75 0.355 74 0.282 73 0.224 72 0.178 710.141 70 0.112 69 0.089 68 0.071 67 0.056 66 0.045 65 0.035 64 0

Thus it can be seen that for each 1° C. increase in water temperaturesabove 80° C., the time-temperature contribution is significantlyincreased. Three seconds at 85° C. is equivalent to over 10 seconds at80° C.

In FIG. 5, the non-linear contribution to the cumulativetime-temperature value, during the single disinfection cycle referred toin the typical temperature profile of FIG. 4, is shown in the maingraph. The main graph has the cumulative time temperature value on theY-axis, and the cycle time (in seconds) on the X-axis. Three distinctperiods of 10, one second samples are represented in charts 510, 520,530, during the disinfection cycle, representing different regions ofthe main graph. The charts 510, 520, 530 show the time-temperature valuecontribution for each second according to the temperature sensed duringthe 1 second intervals.

In chart 510, the 10, one second samples are taken after approximately50 seconds. During the 10 seconds, the water temperature increases from64 to 67° C. This is shown by the line graph corresponding to the watertemperature Y-axis on the left hand side of the chart. The timetemperature contribution at these temperatures is represented by thebars, corresponding to the time temperature Y-axis on the right handside of the chart.

No contribution is made when the water temperature is 64° C. Arelatively small contribution to the time temperature value is made whenthe water temperature is 65 to 67° C. This corresponds to the flatregion of the main graph. Summing the values for the bars indicates thatthe total contribution of the 10, one second intervals is 0.296.Although these contributions are small, they are counted and docontribute to shorten the time required for sanitization. In the priorart, no credit is given for this heating phase.

In chart 520, the 10, one second samples are taken after approximately140 seconds. During the 10 seconds, the water temperature increases from79 to 82° C. This is shown by the line graph corresponding to the watertemperature Y-axis on the left hand side of the chart. The timetemperature contribution at these temperatures is represented by thebars, corresponding to the time temperature Y-axis on the right handside of the chart. Note the difference in scale of the time temperatureY-axis of chart 520 to chart 510.

Increasing contributions to the time temperature value are made as thewater temperature increases from 79 to 82° C. This corresponds to thesteadily increasing region of the main graph. Summing the values for thebars indicates that the total contribution of the 10, one secondintervals is 12.056.

In chart 530, the 10, one second samples are taken after approximately420 seconds. During the 10 seconds, the water temperature increases from83 to 86° C. This is shown by the line graph corresponding to the watertemperature Y-axis on the left hand side of the chart. The timetemperature contribution at these temperatures is represented by thebars, corresponding to the time temperature Y-axis on the right handside of the chart. Note the difference in scale of the time temperatureY-axis of chart 530 to charts 510 and 520.

Greatly increasing contributions to the time temperature value are madeas the water temperature increases from 83 to 86° C. This corresponds tothe steep region of the main graph. Summing the values for the barsindicates that the total contribution of the 10, one second intervals is30.282. Counting the actual contribution to sanitization for the periodsabove 80° C. rather than treating these as the same as 80° C.considerably shortens the required time.

The charts are exemplary in nature only, and different time, temperatureand associated time-temperature values are possible, and indeedenvisaged.

One second intervals have been chosen as a reasonable sampling rate. Thesampling interval could be longer or shorter. A longer sampling intervalwould preferably be associated with a steady temperature profile, whilsta shorter temperature cycle would preferably be associated with greaterprocessing power.

In alternate embodiments of the liquid sanitizer, the processor may beprogrammable. Therefore the threshold temperature may be set manually.For example the threshold temperature may be set to a temperaturebetween 55° C. and 65° C. The overall heating time may be set manually.For example, the heating time may be set to 8, 9 or 10 minutes. In thiscase the processor 230 calculates the necessary temperature profile overthe heating time to ensure the volume of water receives a sanitizingdose.

1. A method of sanitizing liquid for use in a medical device, the methodcomprising the steps of: providing a medical device defining a watercircuit with a volume of liquid; sensing a temperature of the volume ofliquid with a sensor; heating the Volume of liquid from an initialtemperature to exceed a threshold temperature; maintaining the volume ofliquid above the threshold temperature; determining a time-temperaturevalue for the volume of liquid periodically once the thresholdtemperature has been exceeded; calculating a cumulative time-temperaturevalue; and providing an output signal once the cumulativetime-temperature value has reached a level indicative of a sanitizingdose.
 2. The method according to claim 1 wherein the cumulativetime-temperature value is calculated by a processor.
 3. The methodaccording to claim 1 wherein the cumulative time-temperature value iscalculated from a lookup table.
 4. The method according to claim 1,further comprising the step of setting a target cumulativetime-temperature value; and wherein the output signal providing stepcomprises providing the output signal once the target cumulativetime-temperature value is reached.
 5. The method according to claim 4wherein the output signal is in the form of an audible or visual alarm.6. The method according to claim 4 wherein the output signalautomatically causes termination of the liquid heating.
 7. The methodaccording to claim 1, further comprising the step of maintaining thevolume of liquid below an upper temperature.
 8. The method according toclaim 7 comprising the further step of setting the upper temperature. 9.The method according to claim 1, comprising the further step of settingthe threshold temperature.
 10. The method according to claim 1,comprising the further step of setting an overall heating time.
 11. Themethod according to claim 1, wherein the threshold temperature isbetween 55° C. and 65° C.
 12. The method according to claim 7, whereinthe upper temperature is between 70° C. and 99° C.
 13. The methodaccording to claim 1, wherein the sensor comprises multiple temperaturesensors.
 14. The method according to claim 1, wherein the cumulativetime-temperature value A₀ is calculated according to$A_{0} = {\sum{10^{\lbrack\frac{({T - 80})}{z}\rbrack}{dt}}}$ where: anA value is an equivalent time in seconds at 80° C. to give adisinfection effect, z is a change in temperature required to change the<A value by a factor of 10 and A₀ is the A value when z is 10° C.; dt isa chosen time interval, in seconds; T is an average temperature over atime interval di of the volume of liquid in ° C.; and A₀ is a summationfor all of the dt intervals.
 15. The method according to claim 14, wherethe A₀ value is equal to
 1800. 16. A liquid sanitizer defining a liquidcircuit, the liquid sanitizer comprising: a tank for containing a volumeof liquid; a sensor arranged to sense a temperature of the volume ofliquid; a heater arranged to heat the volume of liquid from an initialtemperature to exceed a threshold temperature, and to maintain thevolume of liquid above the threshold temperature; and a processor,wherein the processor is configured to determine a time-temperaturevalue for the volume of liquid periodically once the thresholdtemperature has been exceeded and to calculate a cumulativetime-temperature value so as to provide an output signal once acumulative time-temperature value indicative of a sanitizing dose isreached.
 17. The liquid sanitizer of claim 16, further comprising acartridge that comprises a sanitizing water path that is part of theliquid circuit.
 18. The liquid sanitizer of claim 17, further comprisinga door that allows reception of the cartridge in the liquid sanitizer.19. The liquid sanitizer claim 16, further comprising a pneumatic pumpto pump the liquid through the liquid circuit.
 20. The liquid sanitizerof claim 16, wherein the processor is programmable to alter at least oneof the threshold temperature and the cumulative time-temperature value.21. The liquid sanitizer of claim 16, wherein the processor determinesthe cumulative time-temperature value A₀ according to:$A_{0} = {\sum{10^{\lbrack\frac{({T - 80})}{z}\rbrack}{dt}}}$ where: anA value is an equivalent time in seconds to give a disinfection effect t80° C., z is a change in temperature required to change the A value by afactor of 10, and A₀ is the A value when z is 10° C.: dt is a chosentime interval, in seconds; T an average temperature over a time intervaldt of volume of liquid in ° C.; and A₀ is a summation for all of the dtintervals.
 22. The liquid sanitizer of claim 21 wherein the A₀ value is1800.
 23. The liquid sanitizer of claim 16, wherein the processor isconfigured to set a target cumulative time-temperature value and toprovide the output signal once the target cumulative time-temperaturevalue is reached.
 24. A medical device comprising the liquid sanitizerof claim
 16. 25. A kidney dialyser comprising the liquid sanitizer ofclaim
 16. 26. (canceled)
 27. The liquid sanitizer of claim 16, whereinthe processor is configured to perform at least one of the following:maintaining the volume of liquid below an upper temperature, setting theupper temperature, setting the threshold temperature, and setting anoverall heating temperature.